Successful aortic valve replacement for aortic regurgitation associated with osteogenesis imperfecta.

The occurrence of severe aortic regurgitation in two patients with typical findings of osteogenesis imperfecta is described. Both patients manifested severe haemodynamic abnormalities and underwent successful aortic valve replacement. The operative and pathological findings are discussed.

Effects of intravenous glucose during pacing-induced angina pectoris in patients with coronary artery disease.

The effects of hypertonic glucose infusion on the anginal threshold determined by atrial pacing was studied in 14 patients with significant coronary artery disease. After glucose, angina occurred at a significantly lower heart rate and double product (systolic arterial pressure x heart rate), suggesting a decreased tolerance to ischemic stress. No stoichiometric relationship was noted between glucose uptake and lactate production, and there was no evidence that hypertonic glucose infusion resulted in enhanced anaerobic glycolysis in the ischemic myocardium. Acute elevation of plasma glucose levels may not be beneficial to patients with coronary artery disease.

A population pharmacokinetic analysis of the penetration of the prostate by levofloxacin.

Prostatitis has remained a pathological entity that is difficult to treat. Part of the difficulty revolves about the putative offending pathogens. For acute prostatitis, members of the Enterobacteriaceae, particularly Escherichia coli, play a central role, while intracellular pathogens such as Chlamydia are more frequently seen in chronic prostatitis. Consequently, a drug needs to be able to penetrate to this specialized site in both the acute and chronic infection forms of the disease and also have potent activity against the most common causative pathogens, both intracellular and extracellular. Levofloxacin has such an activity profile. We wished to document its ability to penetrate to the site of infection. Patients undergoing prostatectomies were administered 500 mg of levofloxacin orally every 24 h for 2 days prior to surgery, and then on the day of surgery, 500 mg was administered as an hour-long, constant-rate intravenous (i.v.) infusion. A set of blood samples was obtained as guided by stochastic optimal design theory. Prostate biopsy times were determined by randomizing subjects into one of four groups, based on the interval after the i.v. dose. All plasma and prostate drug concentrations were comodeled by a population modeling program, BigNPEM, implemented on the Cray T3E Supercomputer housed at the Supercomputer Center at the University of California at San Diego. Penetration was determined as the ratio of the area under the concentration-time curve (AUC) of levofloxacin in the prostate to the plasma levofloxacin AUC. When calculated from the mean population parameters, this penetration ratio was 2.96. We also performed a 1,000-subject Monte Carlo simulation from the mean parameter vector and covariance matrix. The mean penetration ratio here was 4.14 with a 95% confidence interval of 0.20 to 19.6. Over 70% of the population had a penetration ratio in excess of 1.0. Levofloxacin adequately penetrates a noninflamed prostate and should be evaluated for the therapy of prostatitis.